October_2021_AMP_Digital

A D V A N C E D M A T E R I A L S & P R O C E S S E S | O C T O B E R 2 0 2 1 2 3 H ydrogels are made of a 3D net- work of crosslinked hydrophil- ic polymers that can absorb and retain large amounts of water and still remain insoluble [1] . Using differ- ent chemical and physical crosslinking strategies, numerous hydrogels have been developed to address a variety of biomedical needs such as 3D cell cul- ture, tissue engineering, controlled drug delivery, and biosensing, among others [2-6] . In order to be suitable for these biomedical applications, hydro- gels need to mimic the native extracel- lular matrix (ECM). The ECM is a fibrous 3D network of proteins and polysaccha- rides that provide cells and tissues with mechanical support, signaling cues, as well as a medium for growth and inter- action. In this regard, hydrogels based on naturally occurring polymers have an advantage over synthetic polymers due to their inherent biocompatibility [7] . One such material is gelatin meth- acrylate (GelMA)—a photopolymer- izable hydrogel derived from gelatin. Gelatin is a biopolymer that is a prod- uct of the hydrolytic degradation of the triple helical tropocollagen rod. Upon heating (> 40 o C), gelatin becomes soluble in water and takes on a ran- domly coiled structure. At a sufficient- ly high concentration, cooling of the solution produces a transparent gel as the gelatin partially recovers its helical structure [8-10] . Of particular interest is the addi- tion of methacrylate groups to the ami- no (-NH 2 ) and hydroxyl (-OH) side chains of gelatin, which impart to it the prop- erty of photo-crosslinking. Upon expo- sure to light and with the presence of a photoinitiator, a hydrogel (i.e., Gel- MA) that is stable at body temperature (37 o C) is formed. The photopolymeriza- tion of GelMA can be spatially and tem- porally controlled. As a result, it can be fabricated into hydrogels with purpose- ful architecture for a variety of biomedi- cal applications [8,9] . GelMA HYDROGEL PREPARATION Although various protocols have been reported for the synthesis of Gel- MA, they are essentially variations of the general method that was first re- ported by Van den Bulcke et al. [8,11,12] In brief, the production of GelMA is a two-step process that involves the deri- vatization of gelatin by methacrylic an- hydride (MA), followed by a crosslinking process. The reaction of methacrylic anhy- dride with gelatin in a phosphate buf- fer (pH = 7.4) solution at 50 o C attaches methacryloyl units to the -NH 3 and -OH groups of gelatin. Diluting the reaction mixture (~5X) with phosphate buffer stops the reaction. To eliminate lowmo- lecular weight impurities, the solution is then dialyzed against deionized wa- ter. This dialyzed solution can be freeze dried and refrigerated until use. Finally, to produce the GelMA hydrogel, a water soluble photoinitiator is added and the solution is irradiated with visible light, ultraviolet light, γ -radiation, or an elec- tron beam to initiate the photopoly- merization process. The most common photoinitiators are 2-hydroxy-1-[4-(2- hydroxyethoxy) phenyl]-2-methyl-1-pro- panone (Irgacure 2959) and lithium acylphosphinate salt (LAP) [8,11,12] . By changing the amount of MA added, different degrees of methacry- loyl substitution can be achieved; this approach produces GelMA with diverse physical properties. In addition, the rate of MA addition and conditions of mix- ing (e.g., pH and temperature) led to changes in the degree of methacryloyl substitution [13,14] . GelMA BIOPRINTING MODALITIES Bioprinting can be achieved through a variety of techniques. These can be broadly classified into extrusion bioprinting, inkjet bioprinting, stereoli- thography, and laser-assisted bioprint- ing. In extrusion bioprinting, a piston, GELATIN METHACRYLATE HYDROGELS FOR 3D BIOPRINTING Because the photopolymerization of gelatin methacrylate can be spatially and temporally controlled, it can be fabricated into hydrogels well suited to a variety of biomedical applications. Pete Gabriel L. Ledesma, University of the Philippines Diliman Kai-Hung Yang, North Carolina State University Roger J. Narayan, FASM,* University of North Carolina and North Carolina State University *Member of ASM International